Dynamical overlap fermions, results with hybrid Monte-Carlo algorithm

We present first, exploratory results of a hybrid Monte-Carlo algorithm for dynamical, n_f=2, four-dimensional QCD with overlap fermions. As expected, the computational requirements are typically two orders of magnitude larger for the dynamical overlap formalism than for the more conventional (Wilson or staggered) formulations.Comment: 13 pages, 2 figure

Relocation of active site carboxylates in major facilitator superfamily multidrug transporter LmrP reveals plasticity in proton interactions

The expression of polyspecific membrane transporters is one important mechanism by which cells can obtain resistance to structurally different antibiotics and cytotoxic agents. These transporters reduce intracellular drug concentrations to subtoxic levels by mediating drug efflux across the cell envelope. The major facilitator superfamily multidrug transporter LmrP from $\textit{Lactococcus}$ lactis catalyses drug efflux in a membrane potential and chemical proton gradient-dependent fashion. To enable the interaction with protons and cationic substrates, LmrP contains catalytic carboxyl residues on the surface of a large interior chamber that is formed by transmembrane helices. These residues co-localise together with polar and aromatic residues, and are predicted to be present in two clusters. To investigate the functional role of the catalytic carboxylates, we generated mutant proteins catalysing membrane potential-independent dye efflux by removing one of the carboxyl residues in Cluster 1. We then relocated this carboxyl residue to six positions on the surface of the interior chamber, and tested for restoration of wildtype energetics. The reinsertion at positions towards Cluster 2 reinstated the membrane potential dependence of dye efflux. Our data uncover a remarkable plasticity in proton interactions in LmrP, which is a consequence of the flexibility in the location of key residues that are responsible for proton/multidrug antiport.A.V.N. is a research associate funded by the Biotechnology and Biological Sciences Research Council (BBSRC). H.S., S.R. and Z.T. received scholarships from the Cambridge Commonwealth, European and International Trust. A.N. is the recipient of a Herchel-Smith Scholarship. K.A. is funded through a programme grant from the Human Frontier Science Program

Small eigenvalues of the staggered Dirac operator in the adjoint representation and Random Matrix Theory

The low-lying spectrum of the Dirac operator is predicted to be universal, within three classes, depending on symmetry properties specified according to random matrix theory. The three universal classes are the orthogonal, unitary and symplectic ensemble. Lattice gauge theory with staggered fermions has verified two of the cases so far, unitary and symplectic, with staggered fermions in the fundamental representation of SU(3) and SU(2). We verify the missing case here, namely orthogonal, with staggered fermions in the adjoint representation of SU(N_c), N_c=2, 3.Comment: 3 pages, revtex, 2 postscript figure

Nonlinear Realization of Chiral Symmetry on the Lattice

We formulate lattice theories in which chiral symmetry is realized nonlinearly on the fermion fields. In this framework the fermion mass term does not break chiral symmetry. This property allows us to use the Wilson term to remove the doubler fermions while maintaining exact chiral symmetry on the lattice. Our lattice formulation enables us to address non-perturbative questions in effective field theories of baryons interacting with pions and in models involving constituent quarks interacting with pions and gluons. We show that a system containing a non-zero density of static baryons interacting with pions can be studied on the lattice without encountering complex action problems. In our formulation one can also decide non-perturbatively if the chiral quark model of Georgi and Manohar provides an appropriate low-energy description of QCD. If so, one could understand why the non-relativistic quark model works.Comment: 34 pages, 2 figures, revised version to be published in J. High Energy Phys. (changes in the 1st paragraph, additional descriptions on the nature of the coordinate singularities in Sec.2, references added

Universal Scaling of the Chiral Condensate in Finite-Volume Gauge Theories

We confront exact analytical predictions for the finite-volume scaling of the chiral condensate with data from quenched lattice gauge theory simulations. Using staggered fermions in both the fundamental and adjoint representations, and gauge groups SU(2) and SU(3), we are able to test simultaneously all of the three chiral universality classes. With overlap fermions we also test the predictions for gauge field sectors of non-zero topological charge. Excellent agreement is found in most cases, and the deviations are understood in the others.Comment: Expanded discussion of overlap fermion results. 17 pages revtex, 7 postscript figure

Gene conversion in human rearranged immunoglobulin genes

Over the past 20 years, many DNA sequences have been published suggesting that all or part of the V<sub>H</sub> segment of a rearranged immunoglobulin gene may be replaced in vivo. Two different mechanisms appear to be operating. One of these is very similar to primary V(D)J recombination, involving the RAG proteins acting upon recombination signal sequences, and this has recently been proven to occur. Other sequences, many of which show partial V<sub>H</sub> replacements with no addition of untemplated nucleotides at the V<sub>H</sub>–V<sub>H</sub> joint, have been proposed to occur by an unusual RAG-mediated recombination with the formation of hybrid (coding-to-signal) joints. These appear to occur in cells already undergoing somatic hypermutation in which, some authors are convinced, RAG genes are silenced. We recently proposed that the latter type of V<sub>H</sub> replacement might occur by homologous recombination initiated by the activity of AID (activation-induced cytidine deaminase), which is essential for somatic hypermutation and gene conversion. The latter has been observed in other species, but not in human Ig genes, so far. In this paper, we present a new analysis of sequences published as examples of the second type of rearrangement. This not only shows that AID recognition motifs occur in recombination regions but also that some sequences show replacement of central sections by a sequence from another gene, similar to gene conversion in the immunoglobulin genes of other species. These observations support the proposal that this type of rearrangement is likely to be AID-mediated rather than RAG-mediated and is consistent with gene conversion

PROlocalizer: integrated web service for protein subcellular localization prediction

Subcellular localization is an important protein property, which is related to function, interactions and other features. As experimental determination of the localization can be tedious, especially for large numbers of proteins, a number of prediction tools have been developed. We developed the PROlocalizer service that integrates 11 individual methods to predict altogether 12 localizations for animal proteins. The method allows the submission of a number of proteins and mutations and generates a detailed informative document of the prediction and obtained results. PROlocalizer is available at http://bioinf.uta.fi/PROlocalizer/

Health States of Exception: unsafe non-care and the (inadvertent) production of ‘bare life’ in complex care transitions

This paper draws on the work of Giorgio Agamben to understand how the social organisation of care transitions can reduce people to their 'bare' life thereby making harmful and degrading treatment seemingly legitimate. The findings of a two-year ethnographic study show how some people experience hospital discharge as undignified, inhumane and unsafe process, expressed through their lack of involvement in care planning, delayed discharge from hospital, and poorly coordinated care. Our analysis explores how these experiences stem from the way patients are constituted as 'unknown' and 'ineligible' subjects and, in turn, how professionals become 'not responsible' for their care. In effect the person is reduce to their 'bare' life with limited value within the care system. We suggest the social productio

Quantum magnetism in two dimensions: From semi-classical N\'eel order to magnetic disorder

This is a review of ground-state features of the s=1/2 Heisenberg antiferromagnet on two-dimensional lattices. A central issue is the interplay of lattice topology (e.g. coordination number, non-equivalent nearest-neighbor bonds, geometric frustration) and quantum fluctuations and their impact on possible long-range order. This article presents a unified summary of all 11 two-dimensional uniform Archimedean lattices which include e.g. the square, triangular and kagome lattice. We find that the ground state of the spin-1/2 Heisenberg antiferromagnet is likely to be semi-classically ordered in most cases. However, the interplay of geometric frustration and quantum fluctuations gives rise to a quantum paramagnetic ground state without semi-classical long-range order on two lattices which are precisely those among the 11 uniform Archimedean lattices with a highly degenerate ground state in the classical limit. The first one is the famous kagome lattice where many low-lying singlet excitations are known to arise in the spin gap. The second lattice is called star lattice and has a clear gap to all excitations. Modification of certain bonds leads to quantum phase transitions which are also discussed briefly. Furthermore, we discuss the magnetization process of the Heisenberg antiferromagnet on the 11 Archimedean lattices, focusing on anomalies like plateaus and a magnetization jump just below the saturation field. As an illustration we discuss the two-dimensional Shastry-Sutherland model which is used to describe SrCu2(BO3)2.Comment: This is now the complete 72-page preprint version of the 2004 review article. This version corrects two further typographic errors (three total with respect to the published version), see page 2 for detail

Lattice gauge theory with baryons at strong coupling

We study the effective Hamiltonian for strong-coupling lattice QCD in the case of non-zero baryon density. In leading order the effective Hamiltonian is a generalized antiferromagnet. For naive fermions, the symmetry is U(4N_f) and the spins belong to a representation that depends on the local baryon number. Next-nearest-neighbor (nnn) terms in the Hamiltonian break the symmetry to U(N_f) x U(N_f). We transform the quantum problem to a Euclidean sigma model which we analyze in a 1/N_c expansion. In the vacuum sector we recover spontaneous breaking of chiral symmetry for the nearest-neighbor and nnn theories. For non-zero baryon density we study the nearest-neighbor theory only, and show that the pattern of spontaneous symmetry breaking depends on the baryon density.Comment: 31 pages, 5 EPS figures. Corrected Eq. (6.1